Relation of olfactory EEG to behavior: Factor analysis.

Rabbits were conditioned to lick (CR+) in response to one odor (CS+); another odor (CS–) served as a discriminative control (CR–). Electroencephalograms (EEGs) were recorded from arrays of 64 electrodes on the olfactory bulb in three stages, each with six sessions: in Stage I, odors A+ and B–; in Stage II, odors C+ and B–; and in Stage III, odors C+ and A–. Spatial EEG amplitude patterns were measured for multiple control (C), CS+, and CS– EEG bursts in each trial. Data were transformed via factor analysis and expressed by factor scores as spatial patterns specified by factor loadings. In discriminant analysis of the factor scores, we correctly classified the C and CS bursts on the average by 65–80% from all trials for each subject and session and by 75–90% for trials with correct CRs. The latter was confirmed with a stepwise linear discriminant analysis of the original 64-variable data. Factor patterns were relatively invariant within but changed between stages. The results implied that stable spatial patterns of bulbar activity emerged in respect to CSs under reinforcement and persisted until the stimulus-response contingencies were changed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Investigation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone for in vivo and iIn vitro murine embryopathy and embryonic ras mutations

The evoked potential recorded in the rat piriform cortex in response to electrical stimulation of the olfactory bulb is composed of an early component occasionally followed by a late component (60-70 ms). We previously showed that the late component occurrence was enhanced following an olfactory learning. In the present study carried out in naive rats, we investigated the precise conditions of induction of this late component, and its spatiotemporal distribution along the olfactory pathways. In the anaesthetized rat, a stimulating electrode was implanted in the olfactory bulb. Four recording electrodes were positioned, respectively, in the olfactory bulb, the anterior and posterior parts of the piriform cortex, and the entorhinal cortex. Simultaneous recording of signals evoked in the four sampled structures in response to stimulation of the olfactory bulb revealed that the late component was detected in anterior and posterior piriform cortex as well as in entorhinal cortex, but not in the olfactory bulb. The late component occurred reliably for a narrow range of low intensities of stimulation delivered at frequencies not exceeding 1 Hz. Comparison of late component amplitude and latency across the different recorded sites showed that this component appeared first and with the greatest amplitude in the posterior piriform cortex. In addition to showing a functional dissociation between anterior and posterior parts of the piriform cortex, these data suggest that the posterior piriform cortex could be the locus of generation of this late high amplitude synchronized activity, which would then propagate to the neighbouring regions.     

Beta-frequency (15-35 Hz) electroencephalogram activities elicited by toluene and electrical stimulation in the behaving rat

Bursts of beta-frequency (15-35 Hz) electroencephalogram activity occur in the olfactory system during odour sampling, but their mode of propagation within the olfactory system and potential contribution to the mechanisms of learning and memory are unclear. We have elicited large-amplitude beta activity in the rat olfactory system by applying noxious olfactory stimuli (toluene), and have monitored the bursts via chronically-implanted electrodes. Following exposure to toluene, coherent bursts with a peak frequency of 19.8 +/- 0.9 Hz were observed in the olfactory bulb, piriform cortex, entorhinal cortex and dentate gyrus. The timing of the bursts and the phases of electroencephalogram cross-spectra indicate that beta bursts propagate in a caudal direction from the olfactory bulb to the entorhinal cortex. The time delays between peaks of bursts in these structures were similar to latency differences for field potentials evoked by olfactory bulb or piriform cortex test-pulses. Peaks of burst cycles in the dentate region, however, were observed just prior to those in the entorhinal cortex. Surprisingly, power in toluene-induced beta-frequency oscillations was not increased following long-term potentiation induced by tetanic stimulation of the olfactory bulb, piriform cortex and entorhinal cortex. The activity of local inhibitory mechanisms may therefore counteract the effects of synaptic enhancements in afferent pathways during beta bursts. Low-frequency electrical stimulation of the piriform cortex was most effective in inducing coherent oscillatory responses in the entorhinal cortex and dentate gyrus at stimulation frequencies between 12 and 16 Hz. The results show that repetitive polysynaptic volleys at frequencies in the beta band induced by either toluene or electrical stimulation are transmitted readily within the olfactory system. The propagation of neural activity within this frequency range may therefore contribute to the transmission of olfactory signals to the hippocampal formation, particularly for those odours which induce high-amplitude bursts of beta activity.     

Relation of olfactory EEG to behavior: Time series analysis.

Measured oscillatory EEG bursts from 64 electrodes implanted on the olfactory bulbs of rabbits. Oscillatory bursts that occurred before and during presentation of odorant conditioned stimuli (CSs) were selected in brief segments. Comparisons between the 64 traces and their spectra showed that despite amplitude differences between channels, every burst had a common waveform over the entire array. The spectra showed 2–5 distinct peaks in each burst. Two types of burst were identified. Those with dominant frequencies greater than 55 Hz had 1 narrow dominant spectral peak and reproducible spatial patterns of its amplitude within subgroups of bursts relating to control and odorant CS conditions. Those with dominant frequencies less than 55 Hz were disorderly, their spectra were broad, and their spatial patterns of amplitude did not reproduce within subgroups. A behavioral assay showed that the high- and not the low-frequency bursts contained odor-specific information. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensory information processing in the frog olfactory pathways. Experimental basis for modeling studies

In the frog, unitary electrophysiological recordings have been extensively used to investigate odor processing along the olfactory pathways. By comparing spontaneous and odor-evoked activities of neuroreceptor, mitral and cortical cells, we have collected fundamental data relating to coding abilities of the three olfactory levels, the olfactory mucosa, the bulb and the cortex. Based on a synthesis of our experimental data related to GABAergic and dopaminergic involvement in the olfactory bulb, this paper aims to match this information with computational data and to discuss some questions on bulbar processing. This paper is also devoted to further analyze original results on coding properties of two functionally evidenced neuron subpopulations in the olfactory cortex. Thus, the assumption according to which some cortical neurons may work as temporal integrators while others as coincidence detectors is presented. Moreover, the pertinence that the neural code may be carried by a single spike with varying latency was demonstrated.     

Potentiation or diminution of discrete motor unconditioned responses (rabbit eyeblink) to an aversive Pavlovian unconditioned stimulus by two associative processes: Conditioned fear and a conditioned diminution of unconditioned stimulus processing.

In 2 experiments using the rabbit conditioned eyeblink preparation, the conditions under which a Pavlovian conditioned stimulus/stimuli (CS) potentiates or diminishes the unconditioned response (UCR) were examined. Results indicate that, after discrimination training (CS+ vs CS–), the CS+ diminished UCR amplitude at the training interstimulus interval (ISI). When CS+ trials were segregated into trials on which a conditioned response (CR) did or did not occur, the CS+ diminished the UCR when it elicited a CR, but not when a CR failed to occur. When the CS-unconditioned stimulus (UCS) interval was lengthened to 10 sec, the CS+ reliably potentiated the eyeblink UCR on CR trials but did not potentiate responding on trials on which a CR was absent. Results are discussed in terms of the modulatory effects and temporal properties of conditioned fear and an associatively produced decrement in UCS processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Atypical olfactory glomeruli subset of the rat: quantitative study and organization of the peripheral afferents

The atypical glomeruli constitute a particular subset of olfactory glomeruli in the rat olfactory bulb which is mainly characterized by a strong centrifugal cholinergic innervation. In the present study, the topographical organization of the mucoso-bulbar projection of these glomeruli was analysed using small injections of WGA-HRP into the anterior nasal cavity of adult rats. The atypical olfactory glomeruli were visualized on adjacent bulbar sections using acetylcholinesterase histochemistry. A mean of 29 atypical glomeruli per bulb was observed in several areas of the posterior half of the olfactory bulb. Following the rostro-caudal axis of the olfactory bulb, the first atypical glomeruli were located in lateral positions, then in dorsal and ventral ones. The most posterior atypical glomeruli were located in the bulbar medial side. Concerning the projections from the periphery to the atypical glomeruli, various WGA-HRP patterns of labelling were observed. When the surface area of injection sites in the anterior part of the olfactory sheet was between 30 and 40 mm2, half of the atypical population was labelled with the atypical glomeruli being heavily labelled. All sites of distribution previously described were represented. When the surface area of injection sites was inferior to 20 mm2, only some positions distributed along the bulbar antero-posterior axis were represented. These atypical glomeruli were generally partially labelled. Taken together, these results suggest that, although atypical glomeruli are restricted in the posterior olfactory bulb, they receive peripheral projections diffusely organized along the antero-posterior axis of the olfactory mucosa. This profile was compared with that of other classical olfactory glomeruli.     

Proliferation, migration and differentiation of neuronal progenitor cells in the adult mouse subventricular zone surgically separated from its olfactory bulb

The subventricular zone of the adult mammalian forebrain contains progenitor cells that, by migrating along a restricted pathway called the 'rostral migratory stream' (RMS), add new neurons to the olfactory bulb throughout life. To determine the influence of the olfactory bulb on the development of these progenitor cells, we performed lesions that interrupt this pathway and separate the olfactory bulb from the rest of the forebrain. By labelling cells born at several survival times after the lesions with the thymidine analogue bromodeoxyuridine (BrdU), we found that disconnection from the bulb influences the rate of BrdU incorporation by the progenitor cells. The number of labelled cells in lesioned mice was almost half that found in control mice. In the disconnected migratory pathway, the number of neurons expressing calretinin was increased indicating that neuronal differentiation was enhanced: newly born neurons occurred within and around the RMS, most of them expressed calretinin and left the pathway starting about 2 weeks after the lesion. Thereafter, these neurons preserving their phenotype, spread for long distances, and accumulated ectopically in dorsal regions of the anterior olfactory nucleus and the frontal cortex. Finally, transplantation of adult subventricular cells into the lesioned pathway showed that the lesion neither prevents neuronal migration nor alters its direction. Thus, although the olfactory bulb appears to regulate the pace of the developmental processes, its disconnection does not prevent the proliferation, migration and phenotypic acquisition of newly generated bulbar interneurons that, since they cannot reach their terminal domains, populate some precise regions of the lesioned adult forebrain.     

Odor processing in the frog olfactory system

In the frog, unitary electrophysiological recordings have been extensively used to investigate odor processing along the olfactory pathways. From the responses of primary second-order neurons, neuroreceptor and mitral cells, odor stimuli could be classified in qualitative groups, revealing that neuronal discriminative mechanisms are partly based on the structure of odor molecule. In the olfactory bulb, thanks both to the anatomical convergence of primary afferences and intrinsic network properties, mitral cells have been demonstrated to gain in odor discrimination and detection power abilities. GABAergic bulbar interneurons were found to be involved in the control of mitral cell excitability, adjusting response thresholds and duration and promoting a progressive increase of burst discharges with stimulus concentration. Otherwise, dopamine was observed to shunt off mitral cell spontaneous activity without altering their odor responsivity properties. Dopamine was demonstrated to act through D2 receptors. Matching anatomical and electrophysiological data, D2 receptors are assumed to be localized on mitral cells. The frog olfactory cortex neurons, silent at rest, could be segregated in two functional groups basing on their odor response properties. The first group shared most intensity coding properties with mitral cells while showing a lower discriminative power, similar to that of neuroreceptor cells. By contrast, the second group provided only minimal intensity coding and, basing on its high discrimination power, was assumed to be mainly devoted to odor discrimination. Thus, along the olfactory pathways, intensity and quality odor parameters which are simultaneously encoded by a neuroreceptor or mitral cell, become specified by two distinct populations in the cortex.     

Olfactory and nonolfactory projections in the river lamprey (Lampetra fluviatilis) telencephalon

The projections of the olfactory bulb, the primordial dorsal, piriform and hippocampal pallia, and of the dorsal thalamus were studied in the lamprey Lampetra fluviatilis using horseradish peroxidase (HRP) and HRP coupled to the wheat germ agglutinin (WGA-HRP). There was obtained an experimental morphological evidence of the presence of the direct thalamo-telencephalic projections in this vertebrate species. The anterior and posterior parts of the dorsal thalamic nucleus, the nucleus of Bellonci, the primordial geniculate bodies, the rostral part of the midbrain were identified as the sources of the telencephalic afferents. These connections may serve as a morphological substrate for transmission of nonolfactory impulses to the telencephalon of the lamprey. The projections of the nucleus of Bellonci into the primordial hippocamp were compared to the limbic thalamo-hippocampal pathways of other vertebrates. We have established, that the fibers ascending from the dorsal thalamus were distributed in the same areas, as those descending from the olfactory bulb. These are: mainly the primordial hippocamp and only a few fibers reach the dorsal and piriform pallia, as well as an area free of olfactory projections--the dorsal part of the subhippocampal lobe. We have also demonstrated that, the secondary olfactory fibers mainly projected ipsilaterally to the primordial dorsal and piriform pallia. A lesser dense bulbar projection has been observed ipsilaterally in the primordial hippocamp and in the ventral part of the subhippocampal lobe. Only few olfactory projections were found in the pallial areas and in the subhippocampal lobe contralaterally. The olfactory fiber terminals were also observed ipsilaterally in the septum, striatum, preoptic area and in the contralateral olfactory bulb. Bilateral bulbofugal projections also occur in the diencephalon, namely in the ventral thalamus and in the hypothalamus. Caudally, the secondary olfactory fibers can be traced up to the area of the posterior tuberculum. Afferents to the olfactory bulb in the river lamprey originate in the subhippocampal lobe, in all three pallial formations and probably in the dorsal thalamus. These structures are at the same time the target zones for the olfactory bulb efferent projections, thus being connected reciprocally with the olfactory bulb.     

Classical conditioning of environmental cues to cigarette smoking.

Smoking-related cues tend to produce urges and cardiac responses in smokers. This reactivity has been assumed to reflect prior classical conditioning. However, little direct evidence exists supporting the notion that environmental cues can be classically conditioned to cigarette smoking. In this study, 8 smokers received 22 daily trials during which 2 cue complexes (comprising visual, olfactory, and auditory stimuli) were paired with smoking (CS+ trials) and not smoking (CS– trials). Reactivity to the environmental cues, as measured by self-report of urge and pulse rate, increased across CS+ trials, diverging from responses in the CS– trials. Reactivity was stronger among light smokers and those who verbalized awareness of smoking contingencies. Findings indicate that environmental cues can be classically conditioned to smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning of relative frequency of sniffing by rabbits to odors.

Developed and evaluated an automated procedure for sniff detection in 4 experiments with 21 adult New Zealand white rabbits. The sniff was identified by a brief episode of increased respiratory rate, usually with a well-defined time of onset. It was detected against the background of respiratory activity in Ss simply, reliably, and noninvasively by statistical evaluation of digitized pneumograph records. The basal rate of exploratory sniffing was controlled by familiarization. Upon conditioning to olfactory cues, the rate of sniffing for CS+ increased sharply above the basal rate during the 1st trials and was maintained at high levels by continued reinforcement. During extinction with discrimination between olfactory cues, the rate for CS– fell sharply at first and then more slowly toward the basal rate. With pseudoconditioning, Ss responded to an unpaired odor after several sessions; the rates of response acquisition and extinction and the maintained level of responding were lower than with a paired odor in classical delayed conditioning, and the response was not discriminative in respect to another novel odor given during extinction. The sniff displayed a prominent sensory bias for olfactory cues. The relative frequencies of sniffing and respiratory slowing were measured as CRs by screening procedures with a small computer. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Deafferentation causes apoptosis in cortical sensory neurons in the adult rat

The present study provides an experimental model of the apoptotic death of pyramidal neurons in rat olfactory cortex after total bulbectomy. Terminal transferase (TdT)-mediated deoxyuridine triphosphate (d-UTP)-biotin nick end labeling (TUNEL), DNA electrophoresis, and neuronal ultrastructure were used to provide evidence of apoptosis; neurons in olfactory cortex were counted by stereology. Maximal TUNEL staining occurred in the piriform cortex between 18 and 26 hr postbulbectomy. Within the survival times used in the present study (up to 48 hr postlesion), cell death was observed exclusively in the piriform cortex; there was no evidence of cell death in any other areas connected with the olfactory bulb. Neurons undergoing apoptosis were pyramidal cells receiving inputs from, but not projecting to, the olfactory bulb. The apical dendrites of these neurons were contacted by large numbers of degenerating axonal terminals. Gel electrophoresis of DNA purified from lesioned olfactory cortex showed a ladder pattern of fragmentation. Inflammatory cells or phagocytes were absent in the environment of degenerating neurons in the early stages of the apoptotic process. The present model suggests that deafferentation injury in sensory systems can cause apoptosis. In addition, olfactory bulbectomy can be used for investigating molecular mechanisms that underlie apoptosis in mature mammalian cortical neurons and for evaluating strategies to prevent the degeneration of cortical neurons.     

Protein synthesis inhibitors delay transneuronal death in the piriform cortex of young adult rats

It has been demonstrated that apoptotic cell death is an active process that is dependent on RNA and protein synthesis. The question remains as to whether neuronal death in adult, mammalian brains can also be demonstrated in vivo to be dependent on protein synthesis. To address this question we have analysed transneuronal death in the piriform (olfactory) cortex. Following unilateral olfactory bulb ablation in young adult rats, layer IIa of the piriform cortex undergoes rapid degeneration, that commences 12 h after ablation and that is almost complete at 48 h. In order to block protein synthesis, three to six subcutaneous injections of the short acting protein synthesis inhibitor anisomycin, were given at 2 h intervals beginning just before the ablation of the olfactory bulb. In other cases a single injection of the long acting protein synthesis inhibitor emetine were made intracerebrally just before or after olfactory bulb ablation. The number of dying cells was then counted in sections through the rostrocaudal extent of the piriform cortex. Both anisomycin and emetine injections markedly reduced the number of pyknotic cells in layer IIa of the piriform cortex after olfactory bulb ablation. The effect of anisomycin was dose-dependent, near lethal doses leading to an almost complete absence of cell death (six injections of 100 mg/kg). As the doses of anisomycin were reduced, more dying cells were observed. Emetine was only effective at near lethal doses (10 mg/kg) and showed a greater capacity to reduce the levels of cell death when injected into structures near the piriform cortex (e.g., accumbens nucleus) than when injected into more distant structures. To further confirm that the cell death observed was due to apoptosis, we analysed sections by tunel staining to demonstrate DNA fragmentation. We found that tunel-positive cells were also always pyknotic, one of the landmarks of apoptosis. The appearance of pyknotic cells labelled by the tunel method demonstrated that the dying cells in the piriform cortex did indeed undergo apoptosis.     

Taste agnosia following gustatory neocortex ablation: Dissociation from odor and generality across taste qualities.

In Exp I, 18 male Long-Evans hooded rats trained to avoid drinking in the presence of a compound odor (benzyl acetate) and taste (sucrose) CS lost the taste habit but retained the odor habit following gustatory neocortex (GN) ablation. Conversely, olfactory bulb ablation resulted in loss of the odor habit but retention of the taste habit. In Exp II, with 60 Ss, Ss lacking GN did not retain preoperatively instated learned aversions to a suprathreshold quinine hydrochloride (bitter) taste solution that had been employed as a CS. However, Ss with GN lesions that were virtually identical to those of the bitter-trained group retained a preoperatively learned aversion to a hydrochloric acid (sour) CS. Exp III, with 60 Ss, demonstrated that reliable agnosia for an acid CS could be produced by lesions that extended more deeply into perirhinal areas near the claustrum at the level of the GN. It is concluded that the agnosia following GN ablation is relatively specific to gustation and that agnosia for preoperatively acquired tasted aversion habits occurs for all 4 basic gustatory stimuli following anterolateral cortex ablations centered on the GN. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial EEG correlates of nonassociative and associative olfactory learning in rabbits.

Recent studies have shown that spatially distributed olfactory bulbar activity correlates with odor-specific behavioral responding (e.g., W. J. Freeman and K. A. Grajski [see PA, Vol 75:28775]; Freeman and W. Schneider [see PA, Vol 68:5257]). The present studies established olfactory bulbar spatial EEG correlates of nonassociative and associative learning in odorant stimulation in rabbits. Behavior was quantified by measuring magnitude and probability of the sniff response. It was shown that (a) olfactory bulbar spatial EEG amplitude patterns do not simply reflect odor (peripheral) stimulation, (b) repeated presentations of a nonreinforced odor initially reveal a transient EEG pattern change but the pattern change does not recur after the subject has habituated to the odor, and (c) repeated presentations of a reinforced odor (mild cutaneous shock), with a second nonreinforced odor serving as a control, reveal that coexisting, odorspecific spatial EEG amplitude patterns emerge with the acquisition of differential behavioral responding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A review on family history of breast cancer: screening and counseling proposals for women with familial (non-hereditary) breast cancer

In a neural model of olfactory bulb processing, we demonstrate the putative role of the modulation of two types of inhibition, inspired by electrophysiological data on the effect of acetylcholine and noradrenaline on olfactory bulb synaptic transmission. Feedback regulation of modulation based on bulbar activity serves to 'normalize' the activity of output neurons in response to different levels of input activities. This mechanism also decreases the overlap between pairs of output patterns (Mitral cell activities), enhancing the discrimination between overlapping olfactory input patterns. The effect of the modulation at the two levels of interneurons is complementary: while an increase in periglomerular inhibition decreases the number of responding output neurons, a decrease in granule cell inhibition increases the firing frequencies of these neurons.     

Olfactory bulb habituation to odor stimuli.

Habituation is a simple form of memory, yet its neurobiological mechanisms are only beginning to be understood in mammals. In the olfactory system, the neural correlates of habituation at a fast experimental timescale involving very short intertrial intervals (tens of seconds) have been shown to depend on synaptic adaptation in olfactory cortex. In contrast, behavioral habituation to odorants on a longer timescale with intertrial intervals of several minutes depends on processes in the olfactory bulb, as demonstrated by pharmacological studies. We here show that behavioral habituation to odorants on this longer timescale has a neuronal activity correlate in the olfactory bulb. Spiking responses of mitral cells in the rat olfactory bulb adapt to, and recover from, repeated odorant stimulation with 5-min intertrial intervals with a time course similar to that of behavioral habituation. Moreover, both the behavioral and neuronal effects of odor habituation require functioning N-methyl-d-aspartic acid receptors in the olfactory bulb. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebellar stimulation as an unconditioned stimulus in classical conditioning.

Implanted rabbits with chronic stimulating electrodes in white matter underlying lobule HVI of the cerebellar cortex. Stimulation elicited movements of the face or neck and, when paired with a tone CS, produced learning comparable to that seen with peripheral unconditioned stimulus/stimuli (UCS). CS-alone trials produced extinction. Reinstatement of paired trials produced reacquisition with savings. Additional groups received either explicitly or randomly unpaired CS–UCS trials before paired conditioning. Low-frequency responding during these sessions indicated that the paired training results were associative and not due to pseudoconditioning or sensitization. Explicitly unpaired sessions retarded learning on subsequent paired trials compared with groups that received either randomly unpaired or no CS–UCS preexposure. These results are interpreted in terms of the role of the cerebellum and associated pathways in classical conditioning of motor responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning with electrical stimulation of cerebellum as both conditioned and unconditioned stimulus.

Stimulating electrodes were implanted in rabbit cerebellum, providing an electrical conditioned stimulus (CS) activating cortical parallel fibers and thence Purkinje and other cells, and an electrical unconditioned stimulus (US) activating underlying white matter and eliciting unconditioned responses. Paired CS-US presentations led to the development of conditioned responses, which showed extinction following CS-alone trials and reacquisition with significant savings on reinstatement of paired trials. Increased local excitability as a result of paired training (but not following unpaired stimulus presentations) was observed in cerebellar cortex, as manifested in substantial decreases in CS threshold for response elicitation in all subjects. This preparation offers a model for the study of plastic neuronal interactions within cerebellar networks critically involved in associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)